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Details

Stereochemistry ACHIRAL
Molecular Formula C16H17FIN3O4
Molecular Weight 461.2268
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AZD-8330

SMILES

CN1C(=O)C(C)=CC(C(=O)NOCCO)=C1NC2=CC=C(I)C=C2F

InChI

InChIKey=RWEVIPRMPFNTLO-UHFFFAOYSA-N
InChI=1S/C16H17FIN3O4/c1-9-7-11(15(23)20-25-6-5-22)14(21(2)16(9)24)19-13-4-3-10(18)8-12(13)17/h3-4,7-8,19,22H,5-6H2,1-2H3,(H,20,23)

HIDE SMILES / InChI

Molecular Formula C16H17FIN3O4
Molecular Weight 461.2268
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

AZD-8330 is a potent, selective, orally active MEK inhibitor that blocks signal transduction pathways implicated in cancer cell proliferation and survival. AZD-8330 has shown tumor suppressive activity in multiple preclinical models of human cancer including melanoma, pancreatic, colon, lung, and breast cancers. AZD-8330 specifically inhibits mitogen-activated protein kinase kinase 1 (MEK or MAP/ERK kinase1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers. AZD-8330 had been in phase I clinical trials by AstraZeneca for the treatment of malignancies. However, this research has been discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
7.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
113.5 ng/mL
20 mg 2 times / day multiple, oral
AZD-8330 plasma
Homo sapiens
160 ng/mL
60 mg 1 times / day multiple, oral
AZD-8330 plasma
Homo sapiens
69.3 ng/mL
20 mg 2 times / day multiple, oral
AZD-8330 plasma
Homo sapiens
160 ng/mL
60 mg 1 times / day single, oral
AZD-8330 plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
252.9 ng × h/mL
20 mg 2 times / day multiple, oral
AZD-8330 plasma
Homo sapiens
351.1 ng × h/mL
60 mg 1 times / day multiple, oral
AZD-8330 plasma
Homo sapiens
186 ng × h/mL
20 mg 2 times / day multiple, oral
AZD-8330 plasma
Homo sapiens
329.8 ng × h/mL
60 mg 1 times / day single, oral
AZD-8330 plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
3.8 h
20 mg 2 times / day multiple, oral
AZD-8330 plasma
Homo sapiens
14.7 h
60 mg 1 times / day single, oral
AZD-8330 plasma
Homo sapiens

PubMed

Sample Use Guides

In Vivo Use Guide
Patients with refractory cancer or cancer with no standard therapy received either once-daily (OD) or twice-daily (BID) oral AZD-8330 on day 1 followed by a 7-day washout period and continuous dosing from day 8. The starting dose was 0.5 mg with dose escalations in subsequent cohorts until a non-tolerated dose was reached. The MTD was defined as 20mg BID.
Route of Administration: Oral
In Vitro Use Guide
AZD-8330 potently and strongly inhibits MEK 1/2. AZD-8330 has no inhibitory activity against over 200 other kinases including at concentrations up to 10 uM. AZD-8330 demonstrates sub-nanomolar potency in mechanistic (pERK) and low to sub-nanomolar potency in functional (proliferation) assays in MEK 1/2 inhibitor sensitive cell lines.
Substance Class Chemical
Record UNII
G4990BOZ66
Record Status Validated (UNII)
Record Version